Upadacitinib counters extraintestinal manifestations in ulcerative colitis

Upadacitinib was more effective than placebo in resolving extraintestinal manifestations (EIMs) in participants with ulcerative colitis (UC) in a phase 3 trial. Induction therapy with upadacitinib initiated the resolution of EIMs, whereas maintenance therapy elicited further improvements. A higher maintenance dose was associated with greater gains than a lower maintenance dose.

EIMs are frequently observed in patients with UC. In addition, these EIMs are challenging to treat and may reduce the quality of life for patients with UC. Since the JAK inhibitor upadacitinib was demonstrated to be safe and efficacious in patients with UC, Prof. Jean-Frédéric Colombel (Icahn School of Medicine at Mount Sinai, NY, USA) aimed to evaluate the impact of upadacitinib on EIMs in participants with moderately to severely active UC [1–4]. Data was included from the phase 3 U-ACHIEVE induction and maintenance trials (NCT02819635) and U-ACCOMPLISH induction trial (NCT03653026).

Peripheral arthropathy, axial arthropathy, and anaemia were the most common EIMs in this population. Data from the induction studies showed that 8 weeks of therapy with 45 mg upadacitinib (n=660) was associated with higher proportions of achieving resolution of EIMs compared with placebo (n=328) (40.0% vs 33.3%). For arthropathies, the corresponding figures were 54.7% and 42.1%. In addition, anaemia was resolved in 38.2% of the participants in the upadacitinib arms and 32.6% of the participants in the placebo arms after 8 weeks of therapy. None of these differences were significant.

At week 52, maintenance therapy with 30 mg upadacitinib (n=154) significantly outperformed placebo (n=149) in the resolution of EIMs (65.9% vs 24.3%; P<0.001). However, 15 mg upadacitinib maintenance therapy (n=148) had no significant benefit over placebo in the resolution of EIMs (41.7% vs 24.3%). Similarly, resolution of arthropathies was significantly more likely to occur in participants in the 30 mg arm compared with participants in the placebo arm (66.7% vs 22.2%; P=0.010), whereas participants in the 15 mg arm showed no significant benefit over placebo (38.5%). Furthermore, in 70.8% of the participants in the 30 mg arm, anaemia was resolved at week 52, compared with 36.4% in the placebo arm (P=0.019). Anaemia was resolved in 50.0% of the participants in the 15 mg arm, but this was not significantly different from placebo (36.4%).

1. Sandborn WJ, et al. Gastroenterology. 2020;158(8):2139–2149.
2. Vermeire S, et al. J Crohns Colitis. 2021;15(Suppl1):S021-S022.
3. Panaccione R, et al. LBA 64, ACG 2021, 22–27 October.
4. Colombel JF, et al. Effect of upadacitinib (UPA) treatment on extraintestinal manifestations (EIMs) in patients with moderate-to-severe Ulcerative Colitis (UC): Results from the UPA Phase 3 programme. OP33, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024